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LECTURE NOTES

                  Dr Nusrat Zareen
             Associate professor Anatomy
                     MBBS; FCPS

        Heart Development I, II, III
Learning Objectives:
       1. Recall the source of heart.
       2. Describe the development of the cardiogenic region
          correlating the process of gastrulation with the changes that
          occur to form a single heart tube in the thorax, and the role
          that embryonic folding plays in this process.
       3. Describe the looping and folding of the heart tube that gives
          rise to the adult location of the developing heart chambers.
       4. Describe the development of the inflow tract.
       5. Describe the development of the atria and the interatrial
          septum.
       6. Describe the development of the atrioventricular valves and
          the aortic and pulmonary valves.
       7. Describe the development of the ventricles and the
          interventricular septum.
       8. Describe the partitioning of the outflow tract and the
          contribution of neural crest cells to this process.
THE THREE LAYERS OF THE HEART

THE ENDOCARDIUM. (Mesodermal- splanchnic mesoderm)

THE MYOCARDIUM. (Mesodermal- splanchnic mesoderm)

THE EPICARDIUM. (Mesodermal)- it is derived from the mesothelial cells from the region of SINUS
VENOSUS migrating over the heart.

The 5 stages to heart development are:
    1. Specification of cardiac precursor cells.

    2. Migration of cardiac precursor cells and fusion of the primordia.

    3. Heart looping .

    4. Heart chamber formation.

    5. Septation and valve formation

There are 02 types of cardiac precursors

                         Splanchnic mesoderm from primitive streak. (Cardiogenic mesoderm at the
                         cranial end of embryonic disc.

                         Out flow portions of the heart from NCC

The cardiogenic cells ingression from the primitive streak & migrate cranially rostral to the neural
plate to form a horse shoe shaped cardiogenic area.




                                                       Horse shoe shaped ---- CARDIOGENIC
                                                       FIELD
ROLE OF NEURAL CREST CELLS




                         The contribution of NCC: Migration and positioning

The cardiac neural crest migrating into the heart region is responsible for forming the entire
musculoconnective tissue wall of the large arteries emerging from the heart, the membranous portion
of the ventricular septum, and the septum between the aorta and pulmonary artery.




                                STAGES OF HEART TUBE FORMATION




The first sign of heart development is the formation of ENDOCARDIAL TUBES/cardiogenic cords.
These tubes fuse to form a single heart tube. This tube then loops and folds and remodel to
finalize the chambering of heart.
Notice the formation of the paired endocardial tubes, derived from the splanchnic mesoderm.
These tubes then fuse to form the single heart tube, suspended in the pericardial cavity. All
encircled.




THE THREE Histological LAYERS OF THE HEART,   all mesodernal
THE ENDOCARDIUM. (Angioblastic Mesoderm derived from splanhnic mesoderm)

THE MYOCARDIUM.(Splanchnic Mesoderm)

THE EPICARDIUM. (Mesoderm derived from the mesothelial cells on the surface of septum trnsversum
migrating over the heart.)




                                       What is cardiac jelly? How is it derive
Buccopharyngeal / oropharyngeal membrane




                                                     As the heart develops, it
                                                     changes its relation to the
                                                     buccopharyngeal membrane.
                                                     What is this changing relation
                                                     and what is the cause of this?




The changed relation is that originally the heart is anterior / cranial to the membrane then it
gradually comes in____________________________ relation to the membrane, and sinks into
the thoracic cavity. (see the figure and fill in the blank.)

The causes of this changing relation are:

   1. Closure of Neural tube.

   2. Formation of brain vesicle

   3. FOLDING OF THE EMBRYO
SUMMARY OF EVENTS - DEVELOPMENT OF PRIMITIVE HEARTTHE
•   The cardiogenic cells in EPIBAST (immediately lateral to Primitive streak) migrate
    through the PRIMITIVE STREAK, proceed cranially and reside in SPLACHNIC layer of
    Lateral Plate mesoderm.
•   The Pharyngeal endoderm beneath the mesoderm induces them to become cardiac
    myoblasts and vascoulognesis also starts.
•   Paired Endothelial strands (THE ANGIOBLASTIC CORDS) form.
•   These cords CANALIZE to form ENDOCARDIAL HEART TUBES (mid 3rd wk)
•   Paired ENDOCARDIAL HEART TUBES fuse to form TUBULAR HEART (late in the 3rd week)
•   HEART BEGINS TO BEAT BY DAY 22- 23 (BEGINNING OF 4RTH WK)
Development time line of heart
Exercise: Summarize the events of heart formation
THE HEART TUBE




                         Cephalic end




Caudal end
                                                      Looping of heart tube
                                                   The fused heart/ endocardial tube begin
                                                  to loop at day 23 and complete at day 28.




        Observe:

             • The cephalic portion moving ventrally, caudally and to the right.
                                                              And
             • The caudal portion looping dorsally, cranially and to the left.
WHAT FORMS FROM WHAT

EMBRYONIC DILATATION          ADULT STRUCTURE

TRUNCUS ARTERIOSUS            Aorta
                              Pulmonary trunk

BULBOUS CORDIS                Smooth part of right ventricle
                              Smooth part of left ventricle



PRIMITIVE VENTRICLE           Trabeculated part of right ventricle
                              Trabeculated part of left ventricle

PRIMITIVE ATRIUM              Trabeculated part of right Atrium
                              Trabeculated part of left Atrium

SINUS VENOSUS                 Smooth part of right Atrium
                              Coronary vein
                              Oblique vein of left Atrium
Circulation route through the heart Tube.
Blood enters the “venous end” (sinus venosus) and leaves through the arterial
end (truncus arterious)

                      UNIDIRECTIIONAL BLOOD FLOW
Blood enters the Sinus venosus - common atrium -AV canal - Common Ventricle -
Bulbous cordis - Truncus arteriosus - Aortic sac - Aortic arches and into Dorsal
aorta.


         Compare the primordia of looped heart and the
              respective adult structures formed
After the looping of the heart tube, internal specifications start taking form. We
shall see the following:
      Fate of Sinus venosus.
      Septae formation / Partitioning of fused endocardial tube:
                   Partitioning of common atrium.
                   Partitioning of Atrioventricular canal.
                   Partitioning of common ventricle.
                   Partitioning of common out flow tract (truncus arteriosus)

The fate of sinus venosus- what forms from it? Observe




                                                         • Absorption of left
                                                           sided veins

                                                         • Formation of oblique
                                                           vein & coronary sinus
                                                           on left

                                                         • Incorporation of right
                                                           horn into the right
                                                           atrium.
Notice the sino artial junction and the veins of the right sinus horn opening into the right atrium
after incorporation of the right horn into it.




The atrioventricular canal septates (DIVIDES):




The common atrioventricular canal is wide communication between the undivided atrium and
ventricle. But due the formation of the endocardial cushions and their fusion (see figure above),
this common AV canal is divided into right and left AV canals. These canals will provide routes
of blood from right and left atria to right and left ventricles after their formations.
THE INTERATRIAL SEPTA - (Wall between the atria)
Following is the shape of the looped heart (tube). Notice the position of the atrium and the
ventricle. Both these chambers are undivided originally with an atrioventricular canal between
them. Later septa develop inside them dividing them into right and left chambers separated by
right and left AV Canals




                              Common atrium



                                                            Position of the Av CANAL where
                                                            endocardial cushion form, dividing it into
                                                            right & left halves

                              Common ventricle




Notice the position of the AV canal (ENDOCARDIAL CUSHIONS) and the position of septae in the
atrium and the ventricle respectively




                                        The interatrial septum develops from the roof of the
                                        atrium and grows towards the endocardial cushions in
                                        the AV canal. The interventricular septum develops
                                        from the floor of the ventricle and grows towards the
                                        endocardial cushions in the AV canal.
The steps of interatrial septum formation:

1. During the 4th week, the septum primum grows from the roof of the primitive
   atrium toward the endocardial cushions. The lower end does not completely descend to
   the cushions leaving a space called osteum primum




2. Later the osteum primum closes off. Vacuoles develop In the septum primum which
   coalesce to form the osteum secundum.




3. Another septum, the septum secundum grows from the roof of the primitive
   atrium toward the endocardial cushions, curtaining off the osteum secundum. This
   septum also leaves a gap – the foramen ovale.
4. The septum primum forms the valve for the foramen ovale which shunts blood from the right to
    the left atrium.

5. This completes the formation of interatrial septa with a defect, the foramen ovale. At birth
    pressure in the left atrium increases and the septum primum flaps close the foramen ovale. So
    the development of interatrial septa completes at birth.




                 ASD: Atrial septum defect. (Patent foramen ovale)
Partition of the conotruncal region- Conus cordis and truncus arteriosus (the out
flow tract) & FORMATION OF AORTICO PULMONARY SEPTUM




   •   Neural crest cells migrate into the outflow tract populating the wall and
       participating/inducing the formation of the septum.

   •   The first indication of a developing septum is the appearance of two ridges
       projecting into the outflow tract from opposite      sides. Curiously, these ridges
       spiral in a counter-clockwise direction up the developing outflow tract.
1. Pair of ridges growing from the opposite walls of the outflow tract.




2. The two ridges grow toward each other spirally and eventually fuse resulting in the
   formation conotruncal       sptum (Aortico pulmonary septum) that divides
   the tract into aorta and the pulmonary trunk.
The spiral pattern results in the apparent curve of the aorta up, over, and behind the
pulmonary trunk seen in the adult.




INTERVENTRICULAR SEPTUM FORMATION
As the interatrial septa are forming, the primitive ventricle is also partitioning.
There are 2 portion s of Intrerventricular septum;
                 Membranous

                 Muscular

1. The forming interventricular septum is initially a muscular partition defining an interventricular
   foramen between its upper border and the fused endocardial cushions.




                                     The muscular ridge- IV
                                     septum
2. A portion of the muscular interventricular septum will eventually fuse to the endocardial
   cushions contributing to the formation of a membranous portion of the interventricular
   septum.
IV septum is contributed by:

                         • Endocardial cushions.
                         • Interventricular septum
                         • Aortico pulmonary septum




____________________________________________________________




        FOR cardiac anomalies consult LANGMAN’S EMBRYOLOGY

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Heart development i

  • 1. LECTURE NOTES Dr Nusrat Zareen Associate professor Anatomy MBBS; FCPS Heart Development I, II, III Learning Objectives: 1. Recall the source of heart. 2. Describe the development of the cardiogenic region correlating the process of gastrulation with the changes that occur to form a single heart tube in the thorax, and the role that embryonic folding plays in this process. 3. Describe the looping and folding of the heart tube that gives rise to the adult location of the developing heart chambers. 4. Describe the development of the inflow tract. 5. Describe the development of the atria and the interatrial septum. 6. Describe the development of the atrioventricular valves and the aortic and pulmonary valves. 7. Describe the development of the ventricles and the interventricular septum. 8. Describe the partitioning of the outflow tract and the contribution of neural crest cells to this process.
  • 2. THE THREE LAYERS OF THE HEART THE ENDOCARDIUM. (Mesodermal- splanchnic mesoderm) THE MYOCARDIUM. (Mesodermal- splanchnic mesoderm) THE EPICARDIUM. (Mesodermal)- it is derived from the mesothelial cells from the region of SINUS VENOSUS migrating over the heart. The 5 stages to heart development are: 1. Specification of cardiac precursor cells. 2. Migration of cardiac precursor cells and fusion of the primordia. 3. Heart looping . 4. Heart chamber formation. 5. Septation and valve formation There are 02 types of cardiac precursors Splanchnic mesoderm from primitive streak. (Cardiogenic mesoderm at the cranial end of embryonic disc. Out flow portions of the heart from NCC The cardiogenic cells ingression from the primitive streak & migrate cranially rostral to the neural plate to form a horse shoe shaped cardiogenic area. Horse shoe shaped ---- CARDIOGENIC FIELD
  • 3. ROLE OF NEURAL CREST CELLS The contribution of NCC: Migration and positioning The cardiac neural crest migrating into the heart region is responsible for forming the entire musculoconnective tissue wall of the large arteries emerging from the heart, the membranous portion of the ventricular septum, and the septum between the aorta and pulmonary artery. STAGES OF HEART TUBE FORMATION The first sign of heart development is the formation of ENDOCARDIAL TUBES/cardiogenic cords. These tubes fuse to form a single heart tube. This tube then loops and folds and remodel to finalize the chambering of heart.
  • 4. Notice the formation of the paired endocardial tubes, derived from the splanchnic mesoderm. These tubes then fuse to form the single heart tube, suspended in the pericardial cavity. All encircled. THE THREE Histological LAYERS OF THE HEART, all mesodernal THE ENDOCARDIUM. (Angioblastic Mesoderm derived from splanhnic mesoderm) THE MYOCARDIUM.(Splanchnic Mesoderm) THE EPICARDIUM. (Mesoderm derived from the mesothelial cells on the surface of septum trnsversum migrating over the heart.) What is cardiac jelly? How is it derive
  • 5. Buccopharyngeal / oropharyngeal membrane As the heart develops, it changes its relation to the buccopharyngeal membrane. What is this changing relation and what is the cause of this? The changed relation is that originally the heart is anterior / cranial to the membrane then it gradually comes in____________________________ relation to the membrane, and sinks into the thoracic cavity. (see the figure and fill in the blank.) The causes of this changing relation are: 1. Closure of Neural tube. 2. Formation of brain vesicle 3. FOLDING OF THE EMBRYO
  • 6. SUMMARY OF EVENTS - DEVELOPMENT OF PRIMITIVE HEARTTHE • The cardiogenic cells in EPIBAST (immediately lateral to Primitive streak) migrate through the PRIMITIVE STREAK, proceed cranially and reside in SPLACHNIC layer of Lateral Plate mesoderm. • The Pharyngeal endoderm beneath the mesoderm induces them to become cardiac myoblasts and vascoulognesis also starts. • Paired Endothelial strands (THE ANGIOBLASTIC CORDS) form. • These cords CANALIZE to form ENDOCARDIAL HEART TUBES (mid 3rd wk) • Paired ENDOCARDIAL HEART TUBES fuse to form TUBULAR HEART (late in the 3rd week) • HEART BEGINS TO BEAT BY DAY 22- 23 (BEGINNING OF 4RTH WK)
  • 8. Exercise: Summarize the events of heart formation
  • 9. THE HEART TUBE Cephalic end Caudal end Looping of heart tube The fused heart/ endocardial tube begin to loop at day 23 and complete at day 28. Observe: • The cephalic portion moving ventrally, caudally and to the right. And • The caudal portion looping dorsally, cranially and to the left.
  • 10. WHAT FORMS FROM WHAT EMBRYONIC DILATATION ADULT STRUCTURE TRUNCUS ARTERIOSUS Aorta Pulmonary trunk BULBOUS CORDIS Smooth part of right ventricle Smooth part of left ventricle PRIMITIVE VENTRICLE Trabeculated part of right ventricle Trabeculated part of left ventricle PRIMITIVE ATRIUM Trabeculated part of right Atrium Trabeculated part of left Atrium SINUS VENOSUS Smooth part of right Atrium Coronary vein Oblique vein of left Atrium
  • 11. Circulation route through the heart Tube. Blood enters the “venous end” (sinus venosus) and leaves through the arterial end (truncus arterious) UNIDIRECTIIONAL BLOOD FLOW Blood enters the Sinus venosus - common atrium -AV canal - Common Ventricle - Bulbous cordis - Truncus arteriosus - Aortic sac - Aortic arches and into Dorsal aorta. Compare the primordia of looped heart and the respective adult structures formed
  • 12. After the looping of the heart tube, internal specifications start taking form. We shall see the following: Fate of Sinus venosus. Septae formation / Partitioning of fused endocardial tube: Partitioning of common atrium. Partitioning of Atrioventricular canal. Partitioning of common ventricle. Partitioning of common out flow tract (truncus arteriosus) The fate of sinus venosus- what forms from it? Observe • Absorption of left sided veins • Formation of oblique vein & coronary sinus on left • Incorporation of right horn into the right atrium.
  • 13. Notice the sino artial junction and the veins of the right sinus horn opening into the right atrium after incorporation of the right horn into it. The atrioventricular canal septates (DIVIDES): The common atrioventricular canal is wide communication between the undivided atrium and ventricle. But due the formation of the endocardial cushions and their fusion (see figure above), this common AV canal is divided into right and left AV canals. These canals will provide routes of blood from right and left atria to right and left ventricles after their formations.
  • 14. THE INTERATRIAL SEPTA - (Wall between the atria) Following is the shape of the looped heart (tube). Notice the position of the atrium and the ventricle. Both these chambers are undivided originally with an atrioventricular canal between them. Later septa develop inside them dividing them into right and left chambers separated by right and left AV Canals Common atrium Position of the Av CANAL where endocardial cushion form, dividing it into right & left halves Common ventricle Notice the position of the AV canal (ENDOCARDIAL CUSHIONS) and the position of septae in the atrium and the ventricle respectively The interatrial septum develops from the roof of the atrium and grows towards the endocardial cushions in the AV canal. The interventricular septum develops from the floor of the ventricle and grows towards the endocardial cushions in the AV canal.
  • 15. The steps of interatrial septum formation: 1. During the 4th week, the septum primum grows from the roof of the primitive atrium toward the endocardial cushions. The lower end does not completely descend to the cushions leaving a space called osteum primum 2. Later the osteum primum closes off. Vacuoles develop In the septum primum which coalesce to form the osteum secundum. 3. Another septum, the septum secundum grows from the roof of the primitive atrium toward the endocardial cushions, curtaining off the osteum secundum. This septum also leaves a gap – the foramen ovale.
  • 16. 4. The septum primum forms the valve for the foramen ovale which shunts blood from the right to the left atrium. 5. This completes the formation of interatrial septa with a defect, the foramen ovale. At birth pressure in the left atrium increases and the septum primum flaps close the foramen ovale. So the development of interatrial septa completes at birth. ASD: Atrial septum defect. (Patent foramen ovale)
  • 17. Partition of the conotruncal region- Conus cordis and truncus arteriosus (the out flow tract) & FORMATION OF AORTICO PULMONARY SEPTUM • Neural crest cells migrate into the outflow tract populating the wall and participating/inducing the formation of the septum. • The first indication of a developing septum is the appearance of two ridges projecting into the outflow tract from opposite sides. Curiously, these ridges spiral in a counter-clockwise direction up the developing outflow tract.
  • 18. 1. Pair of ridges growing from the opposite walls of the outflow tract. 2. The two ridges grow toward each other spirally and eventually fuse resulting in the formation conotruncal sptum (Aortico pulmonary septum) that divides the tract into aorta and the pulmonary trunk.
  • 19. The spiral pattern results in the apparent curve of the aorta up, over, and behind the pulmonary trunk seen in the adult. INTERVENTRICULAR SEPTUM FORMATION As the interatrial septa are forming, the primitive ventricle is also partitioning.
  • 20. There are 2 portion s of Intrerventricular septum; Membranous Muscular 1. The forming interventricular septum is initially a muscular partition defining an interventricular foramen between its upper border and the fused endocardial cushions. The muscular ridge- IV septum 2. A portion of the muscular interventricular septum will eventually fuse to the endocardial cushions contributing to the formation of a membranous portion of the interventricular septum.
  • 21. IV septum is contributed by: • Endocardial cushions. • Interventricular septum • Aortico pulmonary septum ____________________________________________________________ FOR cardiac anomalies consult LANGMAN’S EMBRYOLOGY